1. Field of the Invention
The present invention relates to a method for delivering radiation therapy to a patient to reduce the likelihood of development of restenosis and intimal hyperplasia after an intravascular procedure such as percutaneous transluminal coronary angioplasty (PTCA), and more particularly to an improved method for safely and economically activating a metallic stent to emit radioactivity after it has been deployed within the patient's vasculature.
2. Description of the Prior Art
In PTCA procedures, a guiding catheter having a pre-shaped distal tip is introduced percutaneously into the cardiovascular system of a patient and advanced therein until the pre-shaped distal tip is disposed within the aorta, adjacent to the ostium of the desired coronary artery. The guiding catheter is twisted or torqued from the proximal end to turn the distal tip of the guiding catheter so that it can be guided into the coronary ostium. In an over-the-wire dilatation catheter system, a dilatation catheter having a balloon on its distal end and a guide wire slidably disposed within an inner lumen of the dilatation catheter are introduced into and advanced through the guiding catheter to its distal tip. The distal tip of the guide wire usually is manually shaped (i.e., curved) before the guide wire is introduced into the guiding catheter along with the dilatation catheter. The guide wire usually is first advanced out the distal tip of the guiding catheter, into the patient's coronary artery, and torque is applied to the proximal end of the guide wire, which extends out of the patient, to guide the curved or otherwise shaped distal end of the guide wire as the guide wire is advanced within the coronary anatomy until the distal end of the guide wire enters the desired artery. The advancement of the guide wire within the selected artery continues until its distal end crosses the lesion to be dilated. The dilatation catheter then is advanced out of the distal tip of the guiding catheter, over the previously advanced guide wire, until the balloon on the distal extremity of the dilatation catheter is properly positioned across the lesion. Once properly positioned, the dilatation balloon is inflated to a pre-determined size (preferably the same as the normal inner diameter of the artery at that particular location) with radiopaque liquid at relatively high pressures (e.g., 4.052 to 12.16 bars (4-12 atmospheres)) to dilate the stenosed region of the diseased artery. The balloon then is deflated so that the dilatation catheter can be removed from the dilated stenosis and blood flow can resume through the dilated artery.
A common problem that sometimes occurs after an angioplasty procedure has been performed is the development of restenosis at, or near, the original site of the stenosis. When restenosis occurs, a second angioplasty procedure or even bypass surgery may be required, depending upon the degree of restenosis. It is currently estimated that approximately one third of patients undergoing PTCA procedures develop restenosis within six months. In order to prevent this occurrence and thus obviate the need to perform bypass surgery or subsequent angioplasty procedures, various devices and procedures have been developed for reducing the likelihood of development of restenosis after arterial intervention. For example, an expandable tube (commonly termed a "stent") designed for long term implantation within the body lumen has been utilized to help prevent restenosis. By way of example, several stent devices and stent delivery systems can be found in commonly assigned and commonly owned U.S. Pat. No. 5,158,548 (Lau et al.); U.S. Pat. No. 5,242,399 (Lau et al.); U.S. Pat. No. 5,344,426 (Lau et al.); U.S. Pat. No. 5,421,955 (Lau et al.); U.S. Pat. No. 5,514,154 (Lau et al.); U.S. Pat. No. 5,569,295 (Lam); and U.S. Pat. No. 5,360,401 (Tumlund et al.), which are hereby incorporated herein in their entirety by reference thereto.
More recent devices and procedures for preventing restenosis after arterial intervention employ the use of a radiation source to minimize or destroy proliferating cells which are thought to be a major factor in restenosis development. Balloon catheters have been suggested as a means to deliver and maintain the radiation source in the area where arterial intervention has taken place, exposing the area to a sufficient radiation dose to abate cell proliferation. Two such devices and methods are described in U.S. Pat. No. 5,302,168 (Hess) and U.S. Pat. No. 5,503,613 (Weinberger). Other devices and methods which utilize radiation treatment delivered by an intravascular catheter are disclosed in commonly assigned and commonly owned co-pending U.S. Ser. No. 08/654,698, filed May 29, 1996, entitled Radiation-Emitting Flow-Through Temporary Stent, which is hereby incorporated herein in its entirety by reference thereto.
Another medical device for the treatment of a body lumen by radiation is disclosed in European Patent App. No. 0 688 580 A1 (Schneider). In the Schneider device, the balloon catheter includes a lumen that extends from a proximal opening to an area near the distal end of the catheter, where it dead ends. This lumen, known as a "blind" or "dead end" lumen, is intended to carry a radioactive tipped source wire that slides into the lumen once the catheter is in place in the artery or body lumen. When the source wire is positioned, the radioactive section at the distal tip lies near the dead end to provide radiation to the body lumen.
Another procedure employed to deliver a radiation source to a vessel is disclosed in U.S. Pat. No. 5,503,613 (Weinberger), wherein a catheter is provided with two inner lumens. One lumen accepts a guide wire for sliding into the body lumen. The other lumen is a blind lumen and receives a radiation dose delivery wire manipulated remotely by a computer controlled afterloader. After the catheter has been positioned with its distal end lying just past the stenosed area, the radiation dose delivery wire is inserted into the open end of the blind lumen and advanced to the dead end where it delivers a radiation dose to the affected tissue. This method necessitates a rather large catheter cross section to accommodate both lumens, which can complicate the insertion of the catheter in narrow, tortuous arteries. Another method bypasses this problem by employing an over-the-wire catheter to treat the stenosed region, then withdrawing the guide wire and inserting the radiation dose delivery wire in its place. Unfortunately, with this latter device, the radiation source wire will be exposed to blood, requiring sterilization if reuse is contemplated, or disposal after one use, which is costly and presents radioactive waste disposal issues.
The use of nuclear radiation to prevent restenosis represents a significant improvement in the safety and success rate of PTCA and percutaneous transluminal angioplasty (PTA) procedures. However, a few attendant factors give rise to special considerations that must be addressed to successfully employ this method. In particular, withdrawing the guide wire is disfavored by physicians because it results in a more complex and lengthy procedure, thereby increasing the risk of complications. Furthermore, if the radiation source delivery wire comes in direct contact with the patient's blood, it can cause blood contamination requiring that the radiation wire be sterilized before it is retracted into the afterloader and used on another patient. In addition, the salts and other chemical compounds found in blood may adversely impact the radiation source delivery wire and shorten its useful life.
Another consideration peculiar to intraluminal radiation therapy is that the radiation source must be located centrally within the body lumen being treated to assure uniform delivery of the radiation dose to the entire target area. Typically the radioactive sources employed are gamma ray emitters, and point source gamma rays attenuate inversely with the square of the distance traveled. If the radiation dose delivery wire lies closer to one side of the lumen or at an angle to it, the radiation dose delivered will be nonuniform along the entire length of the target area and some areas can receive appreciably larger doses than others. Achieving such precise spatial alignment of the radiation dose delivery wire is difficult in practice. Although this problem is not encountered when the radiation source is embedded in the tip of the catheter, which is usually centered within the lumen by the inflated balloon, the use of catheters to deliver the radiation dose can result in increased radiation doses being delivered to the body lumens leading to the stenosed area due to the longer insertion time required for catheters. In addition, repeated insertion and withdrawal of catheters can cause additional damage to vascular tissue due to their relatively large cross section.
A group of devices that address most of these problems comprises permanently implantable elements. Fischell, for example, discloses in his U.S. Pat. No. 5,722,984 an intravascular stent with a single layered coating of an antithrombogenic coating that incorporates radioisotopes such as phosphorus 32. The preferred coating is the organic compound phosphorylcholine, the phosphate groups of which contain the radioisotopes. In U.S. Pat. No. 5,713,828, Coniglione discloses a double-walled tubular brachytherapy device with an inner tubular element with an outer surface that incorporates radioactive material. Methods disclosed for incorporating the radioactive material onto this surface include plating, the application of an organic coating such as through solvent evaporation, chemical polymerization, or plastic molding, and neutron irradiation of transmutable, non-radioactive isotopes. The device is intended to be implanted interstitially at the site of a tumor and secured therein with suture material, rigid rods, and other typical surgical connecting members. And in U.S. Pat. No. 5,342,283, Good discloses multilayered devices such as microspheres, ribbons, and wires that include a layer incorporating radioactive materials implanted therein through a host of methods, including plasma sputtering, laser ablation, cathodic arc plasma deposition, ion beam sputtering, ion plating, and neutron irradiation. The devices can be implanted individually or incorporated into other devices such as fabrics.
The permanently implantable radioactive devices disclosed by these patents are advantageous because they can provide much lower doses of radiation upon initial implantation into the patient as compared to temporary devices due to the significantly longer treatment periods over which they emit radiation, and are therefore less likely to affect healthy tissue surrounding the treatment target area. However, the methods disclosed for rendering these devices radioactive suffer from some common shortcomings, most notably the need to prepare the device at a site removed from the hospital such as nuclear reactors for neutron irradiation. This necessitates that the devices be prepared so as to emit relatively high initial levels of radiation in order to account for the natural decay of radioisotopes and ensure that the device is emitting the required level of radiation by the time it is implanted into the patient, which may be days or weeks after the device has been rendered radioactive. This in turn poses increased risks to attending personnel, imposes strict safety measures upon the storage and handling of the devices, and results in much higher cost to the patient. Furthermore, the chemical deposition of radioactive material renders such material more vulnerable to leaching out of the device, and therefore require additional layers to protect the radioactive material from contact with the patient's tissue and blood, thereby further increasing the complexity, size, and cost of these devices, as well as reducing their efficacy due to the radiation shielding effects of such additional layers. The various plasma deposition methods disclosed by Good, on the other hand, require rather elaborate and expensive facilities, as well as lengthy processing times due to the inability of the listed processes to simultaneously implant ions over an object's entire surface; rather, these processes function by extracting ions from a plasma and accelerating them into a beam that is impacted into a typically very small area on the surface of the target. These methods are therefore rather complex and expensive to practice due to the need to manipulate the target object and/or the ion beam in order to adequately and uniformly cover the surface of the target, require relatively longer processing times, and are not particularly well suited to treating irregularly shaped or curved targets.
In light of the above, it becomes apparent that there continues to be a need for a method of delivering radiation therapy to an intravascular area within a patient's body with a device that will emit low levels of radiation over a prolonged period of time and that is safe to handle, and simple and inexpensive to manufacture.